Gigagen, Inc. — Department of Health and Human Services SBIR Phase I: NIAID

Description

<p>DESCRIPTION provided by applicant Recombinant Hyperimmune Gammaglobulin for Pneumococcal Disease Organization GigaGen Inc PI David S Johnson Ph D The Specific Aim of this SBIR Phase I project is to make and test a pilot batch of natural repertoire recombinant Streptococcus pneumonia immunoglobulin rSpIg or andquot hyperimmuneandquot for treatment and prevention of pneumococcal infections Humoral primary immune deficiency PID is a diverse family of disorders including common variable immune deficiency CVID and X linked agammaglobulinemia XLA characterized clinically by recurrent infections Immunologists treat humoral PID with prophylactic intravenous immunoglobulin IVIg which is a pool of proteins isolated from the sera of thousands of donors IVIg reduces pneumococcal infections in CVID and XLA patients by at least Busse et al Bayrakci et al Lucas et al Presumably because andlt of the antibodies in IVIg have activity against pneumococcus Mikolajczyk et al many PID patients require higher IVIg doses to reduce rates of pneumococcal infections Orange et al Tuerlinckx et al A targeted pneumococcal hyperimmune i e a gammaglobulin enriched for anti pneumococcal antibodies might have even higher efficacy without requiring costly doses Previously we developed GigaLink tm Johnson et al which uses microfluidics and multiplexed PCR to build DNA libraries from antibody repertoires with native heavy and light chain immunoglobulin paring intact We market the technology as a research service for big pharma This Phase I SBIR will adapt GigaLink tm specifically to create a recombinant pneumococcal hyperimmune Our technical innovation is to express GigaLinkTM natural human repertoire DNA libraries in a stable CHO expression system To make rSpIg we will first use GigaLinkTM to capture B cells from donors recently vaccinated with Pneumovax r We will then stably express the antibody sequences en masse in CHO to produce an anti pneumococcal hyperimmune protein product The stable CHO can be passaged and used repeatedly to produce thousands of rSpIg protein preps The resulting pneumococcal hyperimmune or rSpIg will first enable clinical innovations that will help patients with immune deficiency or who are otherwise immunocompromised Phase I will demonstrate that we can produce a test batch of rSpIg that shows in vitro activity In Phase II we will take steps to build a cGMP production protocol and perform toxicology pharmacokinetic and efficacy studies on cGMP rSpIg At first rSpIg will act as a pneumococcal booster for conventional IVIg in primary humoral deficiency patients both in chronic and acute settings We also envision that pediatricians would use rSpIg for specific antibody deficiency SAD in children who are refractory to antibiotics Sorensen andamp Moore Finally experts tell us that our technology will also be useful to develop viral hyperimmune gammaglobulins i e for Ebola rapid response PUBLIC HEALTH RELEVANCE Recombinant Hyperimmune Gammaglobulin for Pneumococcal Disease Organization GigaGen Inc PI David S Johnson Ph D Intravenous immunoglobulin is used to treat many kinds of immune disorders and is currently derived from pools of sera from thousands of donors We are building new technology that will allow us to manufacture intravenous immunoglobulin with special activity against bacteria and with less reliance on donors</p>